Names and pronunciation
(kar-mus′teen) BiCNU, Gliadel
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Drug reference
(kar-mus′teen) BiCNU, Gliadel
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Func. class.: Antineoplastic alkylating agent
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Chem. class.: Nitrosourea
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ACTION: Alkylates DNA, RNA; able to inhibit enzymes that allow for the synthesis of amino acids in proteins; activity is not cell-cycle–phase specific
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USES: Brain tumors such as glioblas- toma, medulloblastoma, brainstem gli- oma, astrocytoma, ependymoma, meta- static brain tumors; multiple myeloma (with predniSONE), non-Hodgkin’s dis- C ease, Hodgkin’s disease, other lympho- mas; GI, breast, bronchogenic, renal carcinomas; wafer, as adjunct to surgery/ radiation for patients newly diagnosed with high-grade malignant glioma
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Unlabeled uses: Ablation, mycosis fun- goides, stem cell transplant preparation
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity, leukopenia, thrombocytopenia Precautions: Dental disease, extravasa- tion, females, infection, secondary malig- nancy, thrombocytopenia, renal disease
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Black Box Warning: Bone marrow sup- pression, pulmonary fibrosis, bleeding, infection Black Box Warning: Carmustine should not be given at full dose until platelets >100,000/mm3 and WBC >4000/mm2 Wafer route • Use cytotoxic handling procedures • If wafers are broken into several pieces, they should not be used • Foil pouches may be kept at room temperature for 6 hr if unopened Intermittent IV INFUSION route • Use cytotoxic handling procedures; do not use if an oil film appears on vial (de- composition), use gloves • Do not use with PVC IV tubing, do not admix • After diluting 100 mg product/3 mL ethyl alcohol (provided); dilute with 27 mL of sterile water for injection; then, further dilute with 100-500 mL 0.9% NaCl or D5W, give 250 mL over ≥2 min, reduce rate if discomfort is felt; use only glass contain- ers, protect from light • Flush IV line after carmustine with 10 mL 0.9% NaCl to prevent irritation at site Y-site compatibilities: Amifostine, ampho- tericin B lipid complex, amphotericin B liposome, anidulafungin, aztreonam, bivali- rudin, bleomycin, caspofungin, cefepime, codeine, DAPTOmycin, dexmedetomidine, DOCEtaxel, ertapenem, etoposide, fenoldo- pam, filgrastim, fludarabine, gemcitabine, granisetron, levoFLOXacin, melphalan, meperidine, mitoXANTRONE, nesiritide, octreotide, ondansetron, PACLitaxel, palo- nosetron, pamidronate, pantoprazole, PEMEtrexed, piperacillin-tazobactam, riTUXimab, sargramostim, sodium acetate, tacrolimus, teniposide, thiotepa, tigecy- cline, tirofiban, trastuzumab, vinCRIStine, vinorelbine, voriconazole Black Box Warning: Bone marrow suppression: CBC, differential, platelet count weekly; withhold product if WBC is <4000 or platelet count is <100,000; notify prescriber of results, a lower dose may be needed • Hepatic studies: AST, ALT, bilirubin; monitor regularly; hepatotoxicity occurs rarely • Pregnancy/breastfeeding: identify if pregnancy is planned or suspected, or if breastfeeding; do not use in pregnancy, breastfeeding; contraception should be used Black Box Warning: Pulmonary fibro- sis/infiltrate: pulmonary function tests; chest x-ray films before, during therapy; chest film q2wk during treatment; moni- tor for dyspnea, cough, pulmonary fibrosis; infiltrate occurs after high doses or several low-dose courses (>1400 mg/m2 cumu- lative dose), may occur months or years after treatment Black Box Warning: Only to be used by an experienced clinician in cases of can- cer, immune suppression • Renal studies: BUN, serum uric acid; urine CCr before, during ther- apy; I&O ratio; report fall in urine output of 30 mL/hr, may use allopuri- nol for hyperuricemia with increased fluids • Monitor for cold, cough, fever (may indicate beginning infection) • Bleeding: hematuria, guaiac, bruis- ing, petechiae, mucosa, orifices q8hr • Rinsing of mouth tid-qid with water or club soda; use of sponge brush for sto- matitis • Warm compresses at injection site for inflammation; reduce flow rate if patient complains of burning at infusion site Black Box Warning: To report any changes in breathing or coughing; to avoid smoking • To avoid foods with citric acid, hot temperature, or rough texture if stomati- tis is present; to report any bleeding, white spots, ulceration in mouth to pre- scriber; to examine mouth daily • To avoid aspirin, ibuprofen, razors, commercial mouthwash • To report signs of anemia (fatigue, ir- ritability, shortness of breath, faintness); to report signs of infection (sore throat, fever); pulmonary toxicity can occur up to 15 yr after treatment • Not to receive live vaccines during treatment • That infusion can be painful to veins and that product contains ethanol • To report chest pain • Pregnancy/breastfeeding: to use contraception during treatment; not to breastfeed, discuss product impairing fertility
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SIDE EFFECTS GI: Nausea, vomiting, anorexia, stomatitis, hepatotoxicity GU: Azotemia, renal failure HEMA: Thrombocytopenia, leukopenia, myelosuppression, anemia INTEG: Pain, burning, hyperpigmenta- tion at injection site, alopecia RESP: Fibrosis, pulmonary infiltrate SYST: Secondary malignant neoplastic disease
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INTERACTIONS Increase: bleeding risk—aspirin, antico- agulants, platelet inhibitors Increase: myelosuppression—myelo- suppressive agents, cimetidine Increase: toxicity—other antineoplas- tics, radiation, cimetidine Increase: adverse reactions, decreased antibody reaction—live vaccines Decrease: effects of digoxin, phenytoins Drug/Lab Test Increase: bilirubin, prolactin, uric acid, LFTs Decrease: platelets, WBC, neutrophils, Hct
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DOSAGE AND ROUTES • Adult: IV 75-100 mg/m2 over 1-2 hr × 2 days or 150-200 mg/m2 × 1 dose q6-8wk or 40-75 mg/m2/day × 5 days q6wk INTRACAVITARY up to 8 wafers inserted into resection cavity Nadir dose • Adult: IV Reduce dose by 30% (WBC nadir) 2000-3000 mm3 (platelet nadir) 25000-75000 mm3; reduce dose by 50% (WBC nadir) <2,000 mm3 (platelet nadir) <25,000 mm3 Stem cell transplant/bone marrow ablation (unlabeled) • Adult: IV 450-600 mg/m2 as a single dose or 2 divided doses q12hr at a rate of no more than 3 mg/m2/min
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Available forms: Powder for injection 100 mg; wafer 7.7 mg (intracavitary)
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Administer: • Store reconstituted solution in refrig- erator for 24 hr or at room temperature for 8 hr; protect from light • Blood transfusions, RBC colony-stim- ulating factors to counter anemia • Antiemetic, serotonin antagonists, dexamethasone • All medications PO, if possible; avoid IM injection if platelets are <100,000/mm3
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Assess:
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Evaluate: • Therapeutic response: decreasing size of tumor, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information:
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PHARMACOKINETICS Degraded within 15 min; crosses blood- brain barrier; 70% excreted in urine within 96 hr; 10% excreted as CO2, fate of 20% is unknown
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• Adult: IV 75-100 mg/m2 over 1-2 hr × 2 days or 150-200 mg/m2 × 1 dose q6-8wk or 40-75 mg/m2/day × 5 days q6wk INTRACAVITARY up to 8 wafers inserted into resection cavity Nadir dose
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• Adult: IV Reduce dose by 30% (WBC nadir) 2000-3000 mm3 (platelet nadir) 25000-75000 mm3; reduce dose by 50% (WBC nadir) <2,000 mm3 (platelet nadir) <25,000 mm3 Stem cell transplant/bone marrow ablation (unlabeled)
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• Adult: IV 450-600 mg/m2 as a single dose or 2 divided doses q12hr at a rate of no more than 3 mg/m2/min
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